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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Critical roles of kisspeptins in female puberty and preovulatory gonadotropin surges as revealed by a novel antagonist
Endocrinology, Volume 151, No. 2, Year 2010
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Description
Kisspeptins (Kp) have recently emerged as master regulators of the reproductive axis and among the most potent elicitors of GnRH-gonadotropin secretion. Despite their paramount importance in reproductive physiology and their potential therapeutic implications, development of Kp antagonists has remained elusive, and only recently has the first compound with the ability to block Kp actions in vitro and in vivo, namely p234, been reported. However, previous in vivo studies all used acute central injections, whereas characterization of the effects of the antagonist after continuous or systemic administration, which poses pharmacological challenges, is still pending. We report herein a comprehensive series of analyses on the impact of continuous intracerebroventricular infusion of p234 on puberty onset and the preovulatory surge of gonadotropins in the female rat. In addition, the effects ofsystemic (ip)administrationofataggedp234-penetratin, withapredictedhigherpermeabilityatthe blood-brain barrier, on Kp-10 induced gonadotropin secretion were evaluated. Central infusion of p234 to pubertal females delayed vaginal opening and decreased uterine and ovarian weights at the expected time of puberty, without affecting body weight. Likewise, chronic intracerebroventricular administration of p234 for 4 d prevented the preovulatory surges of LH and FSH. In addition, systemic (ip) administration of p234-penetratin significantly attenuated acute LH and FSH responses to Kp-10, either after intracerebroventricular or ip injection of Kp. Our data document the validity of p234 for antagonizing Kp actions in vivo and provide direct experimental evidence for the important role of Kp signaling in the key events of female reproduction, such as puberty onset and the preovulatory surge of gonadotropins. Copyright © 2010 by The Endocrine Society.
Authors & Co-Authors
Pineda, Rafael
Spain, Cordoba
Universidad de Córdoba
Spain, Madrid
Centro de Investigación Biomédica en Red-fisiopatología de la Obesidad y Nutrición
Roseweir, Antonia Kathryn
United Kingdom, Edinburgh
Mrc Human Reproductive Sciences Unit
Morgan, Kevin
United Kingdom, Edinburgh
Mrc Human Reproductive Sciences Unit
Millar, Robert P.
United Kingdom, Edinburgh
Mrc Human Reproductive Sciences Unit
Tena-Sempere, Manuel
Spain, Cordoba
Universidad de Córdoba
Spain, Madrid
Centro de Investigación Biomédica en Red-fisiopatología de la Obesidad y Nutrición
Spain, Cordoba
Instituto Maimónides de Investigación Biomédica de Córdoba Imibic
Statistics
Citations: 207
Authors: 5
Affiliations: 4
Identifiers
Doi:
10.1210/en.2009-0803
ISSN:
00137227
Research Areas
Sexual And Reproductive Health
Participants Gender
Female